Studies on human retroviruses and oncogenes have been pursued with particular emphasis on their role in human disease. Two subgroups of a human T-cell leukemia virus, designated as HTLV-I and HTLV-II, have the unique capacity to transform human T-cells in vitro, leading to clonal cell populations. Molecular cloning and comparative analyses of the genomes of HTLV-I and HTLV-II, revealed sequence conservation throughout, but particularly in a coding region designated pX and in an enhancer sequence in the viral LTR. These results have direct relevance in the possible mechanism of transformation by these viruses. In addition, variants of HTLV-I with transforming capabilities have been analyzed. Recently, a T-lymphotropic retrovirus (HTLV-III) found in most patients with this disorder has been postulated to be the etiologic agent of the acquired immunodeficiency syndrome (AIDS). Analyses of HTLV-III genome indicate that this virus is related to HTLV-I and -II. A mRNA c-sis oncogene has been cloned from HTLV positive cells (HUT-102). This cDNA clone is 2.8 Kb and appears to include the entire v-sis homologous region and all of the coding sequences. The construction, which includes the SV40 promotor and transcriptional regulatory signals, morphologically transforms NIH 3T3 cells and the transformed cells are highly malignant in nude mice. The DNA sequence of the HUT-102 c-sis is similar to that of normal cells, indicating that the normal c-sis gene contains all the information necessary for malignant transformation. The small envelope protein (p2le) gene of HTLV has been incorporated into a vector which includes a mouse metallothionine promotor and this gene is expressed in mouse fibroblasts. The relationship of HTLV to the expression of extra HLA class I antigens by HTLV-I infected cells has been studied. Using molecular clones of HLA genes and of HTLV it has been observed that sequences coding for the extracellular portion of the class I heavy chain hybridize under conditions which would detect distantly related sequences specific to the pX region of HTLV-I. Studies to put the HTLV pX gene into a mammalian expression vector are in progress.